Ureteroscopy and laser stone fragmentation (URSL) has had recent advancements with the more powerful laser systems with the ability to 'dust' and 'pop-dust' the stone. We wanted to look at the outcomes of this method for large stones (≥ 15 mm) using our new 100 W holmium laser. Over a period of 16 months (January 2017-April 2018), 50 patients underwent URSL for minimum cumulative stone size of ≥ 15 mm. Data were collected prospectively on patient and stone demographics and outcomes of URSL. The laser setting used was a power of 0.3-0.6 J and a frequency of 20-50 Hz using a long-pulse setting with a 272-µm fiber. Fifty patients underwent 55 URSL procedures (5 bilateral procedures) using dusting and pop-dusting settings. The mean age was 58 years (range 2-88 years) with a male:female ratio of 35:15. The mean single and overall stone size were 10.3 mm (3-23 mm) and 21 mm (range 15-52 mm) with two-thirds of all patients (65%) having multiple stones. The stone location was in the kidney (n = 65, 78%), in the ureter (n = 19, 22%) and 5 patients had bilateral renal stones. With a mean operating time of 51 min, the initial and final SFR were 93 and 98%, respectively. A pre-operative stent, access sheath and a post-operative stent were present in 29 (53%), 34 (62%) and 51 (93%) procedures, respectively. Over a mean hospital stay of 0.6 days (74% day-case procedures), there was one Clavien IV complication related to urosepsis but without any other major or minor complications. Dusting and pop-dusting techniques achieve an excellent SFR with low risk of complications even for large stones. This might set a new benchmark for treating large stones, bilateral or multiple stones in a single setting, without the need for secondary procedures in most cases.